Although it is well known that the administration of ethanol can affect nervous system excitability, the cellular basis of such actions is poorly understood. The objective of this project was to characterize the mechanisms regulating nerve cell excitability and the effects of ethanol on those mechanisms. The membrane mechanisms that underlie excitable phenomena were characterized by electrophysiological methods. The membrane ion currents that are involve in the regulation of action potential generation and the steady-state excitability of the membrane have been investigated in neurons from the superior cervical and nodose ganglia and in the hippocampal region of brain. In the neurons from nodose ganglion, two different sodium currents have been characterized, a tetrodotoxin (TTX)-sensitive sodium current and a TTX-resistant sodium current. The TTX-resistant sodium current has a monovalent cation selectivity that is similar to that of the TTX-sensitive sodium current. The TTX-resistant sodium current is less sensitive to divalent cations than the calcium current. These neurons also have two calcium currents, transient and sustained. Investigation of potassium currents in the sympathetic neurons has revealed at least 3 different currents: a voltage-activated transient current, a delayed rectifier current and a sustained calcium-activated current. Similar potassium currents have been characterized in CA3 pyramidal neurons from hippocampus. Studies of transmitter regulation of these currents has revealed that the sustained calcium-activated potassiuim current in hippocampal neurons is inhibited by muscarinic receptor activation, and the calcium current in sympathetic neurons is inhibited by somatostatin. The effect of ethanol is currently being studied on these currents. The significance of the project lies in the fact that the identification of the mechanisms involved in nerve cell excitability and the investigation of the action of ethanol on those mechanisms holds the promise of increasing our understanding of the cellular basis of ethanol's actions in the nervous system.